The PI proposes to utilize his established network of collaborators and methodologies to analyze HIV evolution in patients undergoing HAART. He argues that the effectiveness of this therapy has altered the existing models for viral replication and persistence and that techniques developed for the earlier studies can now be applied to patients on HAART to address the following Specific Aims: 1) evaluate the molecular evolution of viruses in blood as an indicator of whether viruses are suppressed or are continuing to evolve in the face of different selection pressures, 2) determine the impact of HAART on viral env gene evolution in other body compartments/fluids, i.e..- genital secretions (of men and women) and CSF, 3) determine the impact of immune stimulation on virus evolution in patients undergoing concurrent therapy with IL2, 4) determine the origin of viruses attached to lymph node dendritic cells, and 5) determine coreceptor specificity of viruses over time and before and after HAART. For each Specific Aim, collaborators have been identified to provide clinical specimens including blood, semen, vaginal and cervical swabs, CSF, and lymph node biopsies, as well as autopsy samples from occasional patients on HAART who die from complications of advanced immunodeficiency. Plans are also described to correlate these studies of molecular evolution with viral coreceptor utilization and with the decline in the CD4+/CD45RA+ population, which has been proposed by others to decline with the appearance of SI viruses. The PI seeks to provide insight into viral dynamics that are altered in the face of HAART, identify possible reservoirs in the body where viral replication and evolution may continue, and longitudinally provide some insight into parameters that may be associated with the success or failure of HAART.